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Contrasting effects of cardiac glycosides on cisplatin- and etoposide-induced cell death

  • Andrey V. Kulikov , Ekaterina A. Slobodkina , Andrey V. Alekseev , Vladimir Gogvadze and Boris Zhivotovsky EMAIL logo
Published/Copyright: February 6, 2016

Abstract

Cardiac glycosides (CGs) or cardiotonic steroids, which constitute a group of naturally occurring compounds with a steroid-like structure, can act on Na+/K+-ATPase as a receptor and activate intracellular signaling messengers leading to a variety of cellular responses. Epidemiological studies have revealed that CGs, used for the treatment of cardiac disorders, may also be beneficial as anti-cancer agents. CGs, acting in combination with other chemotherapeutic agents, may significantly alter their efficiency in relation to cancer cell elimination, causing both sensitization and an increase in cancer cell death, and in some cases resistance to chemotherapy. Here we show the ability of CGs to modulate apoptotic response to conventionally used anti-cancer drugs. In combination with etoposide, CGs digoxin may enhance cytotoxic potential, thereby allowing the chemotherapeutic dose to be decreased and minimizing toxicity and adverse reactions. Mechanisms behind this event are discussed.

Award Identifier / Grant number: 14-25-00056

Award Identifier / Grant number: 14-04-01660-a and 14-04-31078-mol-a

Funding statement: This work was supported by a grant from the Russian Science Foundation (14-25-00056) (Figures 1–4, 7). The work in the authors’ laboratories is also supported by grants from the Russian Foundation for Basic Research (14-04-01660-a and 14-04-31078-mol-a) and the President of the Russian Federation for young scientists (to A.V.K.) (14.120.14.2849-MK), as well as the Stockholm and Swedish Cancer Societies, the Swedish Childhood Cancer Foundation and the Swedish Research Council.

Acknowledgments:

This work was supported by a grant from the Russian Science Foundation (14-25-00056) (Figures 1–4, 7). The work in the authors’ laboratories is also supported by grants from the Russian Foundation for Basic Research (14-04-01660-a and 14-04-31078-mol-a) and the President of the Russian Federation for young scientists (to A.V.K.) (14.120.14.2849-MK), as well as the Stockholm and Swedish Cancer Societies, the Swedish Childhood Cancer Foundation and the Swedish Research Council.

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Received: 2016-1-4
Accepted: 2016-1-28
Published Online: 2016-2-6
Published in Print: 2016-7-1

©2016 by De Gruyter

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